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Reviews on Environmental Health Jun 2023The association between childhood leukemia and extremely low frequency magnetic fields (ELF-MF) generated by power lines and various electric appliances has been studied... (Meta-Analysis)
Meta-Analysis Review
The association between childhood leukemia and extremely low frequency magnetic fields (ELF-MF) generated by power lines and various electric appliances has been studied extensively during the past 40 years. However, the conditions under which ELF-MF represent a risk factor for leukemia are still unclear. Therefore, we have performed a systematic review and meta-analysis to clarify the relation between ELF-MF from several sources and childhood leukemia. We have systematically searched Medline, Scopus, Cochrane Database of Systematic Review and DARE to identify each article that has examined the relationship between ELF-MF and childhood leukemia. We have performed a global meta-analysis that takes into account the different measures used to assess magnetic field exposure: magnetic flux density measurements (<0.2 µT vs. >0.2 µT), distances between the child's home and power lines (>200 m vs. <200 m) and wire codings (low current configuration vs. high current configuration). Moreover, meta-analyses either based on magnetic flux densities, on proximity to power lines or on wire codings have been performed. The association between electric appliances and childhood leukemia has also been examined. Of the 863 references identified, 38 studies have been included in our systematic review. Our global meta-analysis indicated an association between childhood leukemia and ELF-MF (21 studies, pooled OR=1.26; 95% CI 1.06-1.49), an association mainly explained by the studies conducted before 2000 (earlier studies: pooled OR=1.51; 95% CI 1.26-1.80 vs. later studies: pooled OR=1.04; 95% CI 0.84-1.29). Our meta-analyses based only on magnetic field measurements indicated that the magnetic flux density threshold associated with childhood leukemia is higher than 0.4 µT (12 studies, >0.4 µT: pooled OR=1.37; 95% CI 1.05-1.80; acute lymphoblastic leukemia alone: seven studies, >0.4 µT: pooled OR=1.88; 95% CI 1.31-2.70). Lower magnetic fields were not associated with leukemia (12 studies, 0.1-0.2 µT: pooled OR=1.04; 95% CI 0.88-1.24; 0.2-0.4 µT: pooled OR=1.07; 95% CI 0.87-1.30). Our meta-analyses based only on distances (five studies) showed that the pooled ORs for living within 50 m and 200 m of power lines were 1.11 (95% CI 0.81-1.52) and 0.98 (95% CI 0.85-1.12), respectively. The pooled OR for living within 50 m of power lines and acute lymphoblastic leukemia analyzed separately was 1.44 (95% CI 0.72-2.88). Our meta-analyses based only on wire codings (five studies) indicated that the pooled OR for the very high current configuration (VHCC) was 1.23 (95% CI 0.72-2.10). Finally, the risk of childhood leukemia was increased after exposure to electric blankets (four studies, pooled OR=2.75; 95% CI 1.71-4.42) and, to a lesser extent, electric clocks (four studies, pooled OR=1.27; 95% CI 1.01-1.60). Our results suggest that ELF-MF higher than 0.4 µT can increase the risk of developing leukemia in children, probably acute lymphoblastic leukemia. Prolonged exposure to electric appliances that generate magnetic fields higher than 0.4 µT like electric blankets is associated with a greater risk of childhood leukemia.
Topics: Child; Humans; Electromagnetic Fields; Magnetic Fields; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Cohort Studies; Case-Control Studies; Environmental Exposure
PubMed: 35302721
DOI: 10.1515/reveh-2021-0112 -
Pediatric Blood & Cancer Aug 2015Survivors of pediatric acute lymphoblastic leukemia (ALL) have a significantly higher body mass index (BMI) than their peers. Understanding the critical time periods in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Survivors of pediatric acute lymphoblastic leukemia (ALL) have a significantly higher body mass index (BMI) than their peers. Understanding the critical time periods in which patients with pediatric ALL are vulnerable to unhealthy weight gain will lay the groundwork for developing effectively timed interventions.
PROCEDURE
We determined the growth patterns of patients with pediatric ALL during and after treatment through the conduct of a systematic review and meta-analysis. A search of MEDLINE, Scopus, and Web of Science was performed from its inception through May 2014. Studies met the inclusion criteria if they included at least 10 patients of pediatric ALL, and longitudinally assessed BMI at diagnosis and at least one time point after diagnosis
RESULTS
Twenty-one studies met the inclusion criteria for the systematic review and 16 were included in meta-analysis. The mean increase in BMI z-score during treatment in 1,514 patients with pediatric ALL was 0.81 (95% CI: 0.25-1.38). Specifically, patients experienced substantial weight gain in early treatment (Δ = 0.41, 95% CI: -0.34, 1.17) and again during maintenance (Δ = 0.34, 95% CI:-0.22, 0.90). The mean increase in BMI z-score ranged between 0.52 and 0.89 beyond treatment completion. Subgroup analyses found unhealthy weight gain occurred regardless of patients' receipt of cranial radiation therapy, sex, and, weight status at diagnosis.
CONCLUSIONS
Patients with pediatric ALL experience unhealthy weight gain early in treatment, and increases in weight are maintained beyond treatment completion. Preventing early onset of obesity is a priority for improving the care and outcomes for patients with pediatric ALL.
Topics: Antineoplastic Agents; Body Mass Index; Body Weight; Child; Child, Preschool; Female; Humans; Male; Obesity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survivors; Weight Gain
PubMed: 25808413
DOI: 10.1002/pbc.25519 -
PloS One 2022The incidence of childhood ALL in Indonesia is still largely unknown. The widely mentioned statistics from other countries turn out to be only estimated figures. Other... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence of childhood ALL in Indonesia is still largely unknown. The widely mentioned statistics from other countries turn out to be only estimated figures. Other data do not specify the types of leukemia and are not specifically focused on children. Therefore, this study aims to pool incidence and mortality statistics from available studies in Indonesia.
METHODS
We searched five different academic databases, including Pubmed, MEDLINE, Cochrane Library, Science Direct, and Google Scholar. Three Indonesian databases, such as the Indonesian Scientific Journal Database (ISJD), Neliti, and Indonesia One Search, were also utilized. Incidence was expressed as per 100,000 children. We used the Newcastle-Ottawa scale (NOS) to assess the quality of cohort studies. The inclusion criteria are cohort studies published in the languages of English or Indonesian. For this analysis, we define children as 0-18 years old.
FINDINGS
The incidence rate for childhood ALL was found to be 4.32 per 100,000 children (95% CI 2.65-5.99) with a prediction interval of 1.98 to 9.42 per 100,000 children. The incidence rate is higher in males, with 2.45 per 100,000 children (95% CI 1.98-2.91) and a prediction interval of 1.90 to 3.16 per 100,000 children. As for females, the incidence rate is 2.05 per 100,000 children (95% CI 1.52-2.77) with a prediction interval of 1.52 to 2.77 per 100,000 children. The mortality of childhood ALL ranges from 0.44 to 5.3 deaths per 100,000 children, while the CFR is 3.58% with varying true effect sizes of 2.84% to 4.52%.
INTERPRETATION
With 79.5 million children living in Indonesia in 2018, this means that there were roughly 3,434 new cases of childhood ALL. An organized effort between multiple sectors is needed to improve the registries of childhood ALL in Indonesia.
Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Female; Humans; Incidence; Indonesia; Infant; Infant, Newborn; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Registries
PubMed: 35696384
DOI: 10.1371/journal.pone.0269706 -
Advances in Therapy Dec 2023Clofarabine monotherapy at a dose of 52 mg/m per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL)... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Clofarabine monotherapy at a dose of 52 mg/m per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL) in patients aged 1-21 years after at least two prior regimens. To address a post-marketing requirement for additional evidence of the clinical benefit of clofarabine in its approved indication, a meta-analysis of patient-level data was conducted.
METHODS
A systematic literature review was conducted, using the Dr.Evidence software platform, DOC Search, and Embase, to identify clinical trials with patients with R/R ALL who received clofarabine monotherapy at 52 mg/m. The primary endpoint was complete remission (CR). Secondary endpoints were overall remission (OR, defined by CR or CR with either incomplete platelet recovery or incomplete neutrophil and platelet recovery), duration of response, overall survival (OS), and safety.
RESULTS
A total of 754 patients in 12 clinical studies were analyzed including 682 patients with R/R ALL treated with clofarabine monotherapy at 52 mg/m; of them, 374 were aged < 22 years (pediatric population). Rates of CR and OR were 16% (95% confidence interval [CI] 7, 26) and 28% (95% CI 20, 37), respectively, in the pediatric population and 12% (95% CI 5, 21) and 21% (95% CI 13, 31) in the overall population. Median OS (evaluable in three studies in pediatric patients) was 3.7 months (95% CI 0.1, 31.4), reaching 10.1 months (95% CI 0.3, 68.9) for those achieving OR. Sensitivity analyses supported these findings. The most frequent grade 3-4 adverse events were liver abnormalities, anemia, diarrhea, and febrile neutropenia.
CONCLUSION
In this meta-analysis, CR duration and median OS in pediatric patients with R/R ALL appeared to be slightly longer than in the phase II study. No new safety signals were identified. Results support the use of clofarabine monotherapy in its approved indication.
Topics: Child; Humans; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Clofarabine; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Clinical Trials as Topic
PubMed: 37819554
DOI: 10.1007/s12325-023-02696-7 -
Leukemia Dec 2023In the absence of randomized controlled trials comparing tisagenlecleucel vs. standard of care (SOC) in pediatric and young adult patients with relapsed or refractory...
In the absence of randomized controlled trials comparing tisagenlecleucel vs. standard of care (SOC) in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (r/r ALL), the objective was to compare the efficacy of tisagenlecleucel with historical controls from multiple disease registries using patient-level adjustment of the historical controls. The analysis is based on patient-level data of three tisagenlecleucel studies (ELIANA, ENSIGN and CCTL019B2001X) vs. three registries in Germany/Austria. Statistical analyses were fully pre-specified and propensity score weighting of the historical controls by fine stratification weights was used to adjust for relevant confounders identified by systematic literature review. Results showed high comparability of cohorts after adjustment with absolute SMD ≤ 0.1 for all pre-specified confounders and favorable outcomes for tisagenlecleucel compared to SOC for all examined endpoints. Hazard ratios for OS, EFS and RFS were 0.54 (95% CI: 0.41-0.71, p < 0.001), 0.67 (0.52-0.86, p = 0.001) and 0.77 (0.51-1.18, p = 0.233). The OS, EFS and RFS survival probability at 2 years was 59.49% for tisagenlecleucel vs. 36.16% for SOC population, 42.31% vs. 30.23% and 59.60% vs. 54.57%, respectively. Odds ratio for ORR was 1.99 (1.33-2.97, p < 0.001). Results for OS and ORR were statistically significant after adjustment for confounders and provide evidence supporting a superiority of tisagenlecleucel in r/r ALL given the good comparability of cohorts after adjustment for confounders.
Topics: Humans; Child; Young Adult; Standard of Care; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Austria; Immunotherapy, Adoptive
PubMed: 37880478
DOI: 10.1038/s41375-023-02042-4 -
Haematologica Apr 20246-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene... (Meta-Analysis)
Meta-Analysis
Association of gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.
Topics: Humans; Mercaptopurine; Pyrophosphatases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polymorphism, Genetic; Neutropenia; Treatment Outcome; Chemical and Drug Induced Liver Injury
PubMed: 37794799
DOI: 10.3324/haematol.2023.282761 -
Haematologica Oct 2019Minimal (or 'measurable') residual disease in acute lymphoblastic leukemia appears to be a prognostic indicator, with potential value in informing individualized... (Meta-Analysis)
Meta-Analysis
Minimal (or 'measurable') residual disease in acute lymphoblastic leukemia appears to be a prognostic indicator, with potential value in informing individualized treatment decisions. Complete understanding of the strength of the association between minimal residual disease and long-term outcomes is, however, lacking. A systematic literature review and meta-analysis were performed to elucidate the clinical significance of minimal residual disease with respect to relapse-free survival and overall survival in precursor B-cell acute lymphoblastic leukemia. A total of 23 articles and abstracts, most published between 2012 and 2016, were identified for inclusion in the primary meta-analysis. Typically, patients were in their first complete remission at the time of minimal residual disease assessment; in two studies, all patients were in their second, or later, complete remission. The primary analysis revealed improved relapse-free survival across all studies for patients who achieved minimal residual disease negativity (random effects hazard ratio, 2.34; 95% confidence interval, 1.91-2.86). Improved overall survival for patients who achieved minimal residual disease negativity was also observed (hazard ratio, 2.19; 95% confidence interval, 1.63-2.94). There was no observed difference in the impact of minimal residual disease status in subgroups based on disease stage, minimal residual disease sensitivity threshold level, Philadelphia chromosome status, histological phenotype, risk group, minimal residual disease testing location, minimal residual disease timing after induction, or minimal residual disease detection method. Despite heterogeneity in study design and patient populations between the contributing studies, these data provide a compelling argument for minimal residual disease as a clinical tool for assessing prognosis and guiding treatment decisions in precursor B-cell acute lymphoblastic leukemia.
Topics: Adult; Humans; Neoplasm, Residual; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Remission Induction
PubMed: 30890593
DOI: 10.3324/haematol.2018.201053 -
Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796 -
Journal of Pediatric Hematology/oncology Jan 2020Current evidence regarding the association between paternal smoking before conception or during pregnancy and the risk of childhood acute lymphoblastic leukemia (ALL)... (Meta-Analysis)
Meta-Analysis
Paternal Smoking Before Conception and During Pregnancy Is Associated With an Increased Risk of Childhood Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis of 17 Case-Control Studies.
OBJECTIVE
Current evidence regarding the association between paternal smoking before conception or during pregnancy and the risk of childhood acute lymphoblastic leukemia (ALL) are inconsistent. We aimed to systematically summarize the current evidence regarding this potential association.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE), we systematically retrieved PubMed, Embase, Web of Science, and Scopus, screened relevant literature, and assessed the methodologic quality of the included studies. We calculated the pooled estimates using random-effects models. We assessed statistical heterogeneity by I values and χ tests for the Cochrane Q statistic. We further investigate the dose-response relation using 2-stage nonlinear models.
RESULTS
A total of 17 case-control studies were identified, and the synthesized risk ratios (RRs) for smoking before conception (RR=1.15, 95% confidence interval: 1.04-1.27) and during pregnancy (RR=1.20, 95% confidence interval: 1.12-1.28) were both statistically significant. Moreover, the dose-response analysis showed a positive association as well.
CONCLUSION
Current evidence from observational studies suggests the association between paternal smoking before conception or during pregnancy and the increased risk of childhood ALL, which needs to be confirmed in prospective studies.
Topics: Case-Control Studies; Female; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Smoking
PubMed: 31743318
DOI: 10.1097/MPH.0000000000001657 -
JNCI Cancer Spectrum Oct 2021The effect of chemotherapy on brain development in long-term survivors of pediatric acute lymphoblastic leukemia (ALL) was systematically reviewed.
BACKGROUND
The effect of chemotherapy on brain development in long-term survivors of pediatric acute lymphoblastic leukemia (ALL) was systematically reviewed.
METHODS
A systematic search of Pubmed, Scopus, and PsycINFO databases was conducted to identify articles published between January 2000 and February 2020 that implemented magnetic resonance imaging to assess brain structure and function in pediatric ALL survivors (diagnosed younger than 21 years of age). The review included articles that were published on children diagnosed with ALL between 0 and 21 years of age and treated with chemotherapy-only protocols. Articles meeting the inclusion criteria described survivors on average of 5 years or more from diagnosis and were peer-reviewed articles and original studies.
RESULTS
The search yielded 1975 articles with 23 articles meeting inclusion criteria. The review revealed that survivors had statistically significant alterations in brain anatomy, most commonly a smaller hippocampus and impaired microstructural white matter integrity in frontal brain regions. Survivors also had impaired brain function including lower brain network efficiency and altered resting state connectivity. Survivors also displayed widespread reductions in brain activation (ie, frontal, temporal, parietal brain regions) during cognitive tasks.
CONCLUSION
Although the neurotoxic effects of cancer treatment are reduced in the absence of cranial radiation, survivors treated on chemotherapy-only protocols still display long-term alterations in brain structure and function, which contribute to lifelong neurocognitive late effects.
Topics: Adolescent; Brain; Cancer Survivors; Child; Child, Preschool; Diffusion Magnetic Resonance Imaging; Frontal Lobe; Functional Neuroimaging; Hippocampus; Humans; Infant; Infant, Newborn; Precursor Cell Lymphoblastic Leukemia-Lymphoma; White Matter; Young Adult
PubMed: 34514328
DOI: 10.1093/jncics/pkab069